Analysis of the burden and economic impact of digestive diseases and investigation of research gaps and priorities in the field of digestive health in the European Region—White Book 2: Executive summary

Despite their substantial burden, many digestive diseases are poorly understood, attracting relatively little attention in terms of policy, funding or research. United European Gastroenterology (UEG) commissioned the first White Book, published in 2014, which revealed important insights regarding the public health and economic burden of digestive disorders and health services across Europe. In order to evaluate the current status, increase political and public awareness of digestive disorders and encourage digestive health research, UEG commissioned the White Book 2. The White Book 2 updates analysis of the burden and determinants of digestive disorders, and explores unmet needs for digestive health research. It consists of two parts. Part 1 provides an international comparative analysis of the public health burden of digestive diseases and cancers, and analysis of the economic impact of digestive diseases amongst UEG national society member countries. In Part 2, research gaps and priorities in the field of digestive health are explored by consulting UEG national society members and examining distributions of research activity and European Commission funding for digestive disease related research. It is intended that the findings from these reports will assist UEG in accelerating progress in reducing the burden of digestive disorders, and in identifying priority areas where research and investment are required. It is also hoped that the reports will be of interest to others, including national and specialist gastroenterology societies and policymakers. An overview of the objectives and key findings of the reports are summarised below. The full reports are available via the UEG website and can be accessed here: ueg.eu/white‐book2‐part1 and ueg.eu/white‐book2‐part2 (please see Appendix for details).


INTRODUCTION
Despite their substantial burden, many digestive diseases are poorly understood, attracting relatively little attention in terms of policy, funding or research. 1 United European Gastroenterology (UEG) commissioned the first White Book, published in 2014, which revealed important insights regarding the public health and economic burden of digestive disorders and health services across Europe. 2,3 In order to evaluate the current status, increase political and public awareness of digestive disorders and encourage digestive health research, UEG commissioned the White Book 2.
The White Book 2 updates analysis of the burden and determinants of digestive disorders, and explores unmet needs for digestive health research. It consists of two parts. Part 1 provides an international comparative analysis of the public health burden of digestive diseases and cancers, and analysis of the economic impact of digestive diseases amongst UEG national society member countries.
In Part 2, research gaps and priorities in the field of digestive health are explored by consulting UEG national society members and examining distributions of research activity and European Commission funding for digestive disease related research.
It is intended that the findings from these reports will assist UEG in accelerating progress in reducing the burden of digestive disorders, and in identifying priority areas where research and investment are required. It is also hoped that the reports will be of interest to others, including national and specialist gastroenterology societies and policymakers. An overview of the objectives and key findings of the reports are summarised below. The full reports are available via the UEG website and can be accessed here: ueg.eu/white-book2-part1 and ueg.eu/white-book2-part2 (please see Appendix for details).

Public health burden of digestive diseases and cancers
To explore the changing epidemiology of digestive disorders, an international comparative analysis examining variations in estimates of burden was performed for 44 UEG member countries, located within Europe and the Mediterranean area. Estimates produced by the Global Burden of Disease Study (GBD) 2019 4 were utilised, alongside data obtained from published literature. � Egypt has the highest age-standardised DALY rate for digestive diseases of the member countries ( Figure 1) which is to a large extent attributable to the high burden of liver disease due to viral hepatitis experienced within the country.

Economic impact assessment
To investigate the economic value of reducing the burden of digestive diseases, disease specific measures of indirect and inpatient health service delivery costs were estimated for 31 UEG member countries, mostly located within Europe, for which data were available.

Key findings:
� On average, the estimated cost of inpatient health service delivery (excluding treatment and diagnostics) for digestive diseases as a percentage of Gross Domestic Product (GDP) was 0.12% across the 31 countries.
� Based on past trends (using data up to 2019), inpatient health service delivery costs for digestive diseases are expected to decrease in many countries by the year 2035, possibly related to policies designed to improve efficiency in health service delivery in general. For some countries, however, inpatient health service delivery costs for digestive diseases are anticipated to increase.
� Estimated costs of lost output due to digestive disease related morbidity and premature mortality as a percentage of GDP were, on average, 0.22% and 0.25%, respectively across the 31 countries.

Opportunities to reduce the burden
The overall lack of progress over the last 2 decades in reducing the incidence of digestive disorders underscores the need for greater adoption of effective preventative strategies amongst UEG member countries. To provide insights into evolving challenges and where the greatest health gains can be made, an examination of the proportion of digestive disorder burden attributable to modifiable risk factors was performed using GBD 2019 estimates, including an analysis of the relationship between human development and the burden of digestive disorders among European UEG member countries.
Key findings: � Alcohol use contributes towards a large share of the overall burden of digestive disorders amongst UEG member countries.
Whilst some progress has been made to reduce alcohol related burden, since the year 2000 several countries have experienced increases in the proportion of burden attributable to alcohol use for disorders such as liver disease, pancreatitis, liver cancer, oesophageal cancer, and colon and rectum cancer. as rising inflation will likely exacerbate existing health inequalities, with implications for digestive health. As more data become available, an important avenue for future research will be to assess the impact of the COVID-19 pandemic and its consequences on the burden of digestive disorders and socioeconomic inequalities in the burden within UEG member countries. ROSE ET AL. -661

Survey of the research priorities and preferences of UEG national society members
To gain the views of UEG national society members whilst creating an opportunity for national societies to communicate their research priorities to UEG and other societies, an online survey was conducted. The survey collected information on prioritised research topics and digestive disorders, and asked societies to rank the research areas previously identified as research priorities by UEG's specialist society members 5 across three domains.
Key findings: � In total, 33 responses to the survey were received from UEG national society members-a response rate of 73%. The 33 societies submitted 120 research priorities.
� The most prioritised research topics included drug therapy, diagnosis, and disease prevention research.
� The most prioritised disease categories included inflammatory bowel disease, digestive cancers, chronic liver diseases, diseases of the pancreas, and irritable bowel syndrome.
� Overall, inflammatory bowel disease drug therapy research was the most popular disease and topic combination identified for prioritisation by the societies, followed by digestive cancer prevention research.
� Of the research areas previously identified as research priorities by UEG's specialist society members, life-style/nutrition/diet/ obesity and primary prevention were, on average, the most highly ranked research areas in terms of relevancy to national health policy or national goals. � EU trials/epidemiological studies/networks/surveys and primary prevention were, on average, the most highly ranked research areas in terms of the feasibility of conducting research in these areas.
� EU trials/epidemiological studies/networks/surveys and precision/ personalised medicine were, on average, the most highly ranked research areas in terms of the potential to strengthen collaboration between partners from different organisations, disciplines or sectors.

Distribution of research activity in the field of digestive health
To capture areas where research attention has been focused a bibliometric analysis was used to estimate quantities of published literature indexed within the MEDLINE database by topic and digestive disorder, and to identify areas that appeared underresearched in relation to disease burden. � Of the digestive cancers that were available to analyse, colon and rectum cancer and pancreatic cancer appeared to be under-funded in relation to burden compared with some non-digestive system related cancers.

Recommendations for further research
� The analysis presented in the report is exploratory and intended to be used to initiate further discussions and more detailed investigations to further assist UEG in designing research agendas and advocacy strategies that are responsive to health needs and salient evidence gaps in the field of digestive health.
� Prioritised disease areas that appear under-funded or underresearched may represent research gaps that warrant greater consideration. Digestive diseases, such as irritable bowel syndrome, pancreatitis, and alcohol-related liver disease, which received little in the way of Horizon 2020 research funding were highlighted as areas for prioritisation by the national societies. Additionally, disease prevention research appeared to be under-researched yet regarded as an important area for prioritisation and may represent a promising avenue for development.
� Due consideration must be afforded to developing equitable research agendas and investment strategies given the low levels of research activity and funding for alcohol-related liver disease-a condition which disproportionately burdens more socioeconomically disadvantaged groups, contributing to health inequities.

F I G U R E 2
Relationship between European Commission funding for Horizon 2020 research projects and disease burden in the European Union (measured as Disability-Adjusted Life Years) ROSE ET AL.
-663 � Refinement of the potential areas for prioritisation that have been identified, into specific research questions for investigation can be achieved using systematic review methods and/or focused priority setting exercises.
� Gaining insight from patient groups who represent the intended beneficiaries of the research will be particularly informative.
Capturing the views of marginalised and disadvantaged patient groups who may be more difficult to engage but likely have greater unmet health needs is especially important to inform decisions regarding avenues for further research.
� Additionally, further investigations are needed to identify barriers to conducting research in neglected areas, which will inform the development of effective strategies to encourage increased research activity and funding.
� Institutional body funding could be oriented not only at research grants but also for networking pan-European activities with capacity-building objectives which may provide long-term benefits for digestive health research.
� Coordinated approaches to improve the surveillance of research activity and funding could also support research efforts by helping the research community to identify under-researched areas and opportunities for collaboration.